Biomedical subjects

I Anghelescu

Publications and source records attributed to I Anghelescu.

29 records · Page 2Linked to original sources

PubMed2000

Carbohydrate-deficient transferrin (CDT) and HDL cholesterol (HDL) are highly correlated in male alcohol dependent patients.

BACKGROUND: Serum levels of total HDL cholesterol (HDL) are reportedly influenced by recent alcohol intake. We examined the correlation between HDL cholesterol and widely used markers of excessive alcohol intake, such as carbohydrate-deficient transferrin (CDT), gamma-glutamyl-transferase (GGT), or mean corpuscular volume of erythrocytes (MCV), of which CDT is thought to be the most specific. METHODS: Several serological markers [i.e., CDT, GGT, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), MCV, and HDL] were determined in 100 actively drinking male patients with alcohol dependence (DSM-IV) and in 27 non-alcohol-dependent controls, according to routine procedures. Spearman's rank correlation coefficients were calculated. RESULTS: We found a highly significant positive correlation between HDL and CDT (r(s) = 0.55; p < 0.0005) in patients, but not in controls (r(s) = 0.13;p = 0.51). HDL was also positively correlated with GGT, ALAT, ASAT, and MCV only in patients. CONCLUSIONS: HDL cholesterol, as a widely determined parameter, may represent a useful routine marker for recent excessive alcohol intake. High HDL cholesterol levels should alert clinicians to investigate a patient's recent pattern of alcohol consumption.

Adolescent↗

PubMed1999

Neuroendocrine response to antipsychotics: effects of drug type and gender.

BACKGROUND: To study the influences of drug type and gender on the neuroendocrine response to neuroleptic treatment, we compared the endocrine actions of two neuroleptics with different receptor affinity profiles--a substituted benzamide, amisulpride, a selective D2-like dopamine antagonist; and a thioxanthene, flupenthixol, a mixed D1/D2-like antagonist also blocking serotonin, H1, and D1 receptors--on anterior pituitary hormone secretion in schizophrenic patients (DSM-III-R). METHODS: Blood was withdrawn at 15-min intervals to assess basal secretion of prolactin, growth hormone (GH), and thyroid-stimulating hormone (TSH). Four hundred micrograms of thyrotropin-releasing hormone (TRH) was injected i.v. to investigate drug effects on TRH-stimulated secretion of prolactin, TSH, and GH. RESULTS: Prolactin plasma levels were markedly elevated in both treatment groups. In female, but not in male patients, this elevation was significantly more pronounced under amisulpride than under flupenthixol. The prolactin response to TRH was significantly blunted by amisulpride only in male subjects. While basal TSH secretion was significantly increased by both compounds, TRH-stimulated TSH secretion was elevated only in patients treated with amisulpride. Low basal prolactin levels predicted improvement of negative symptoms in patients treated with amisulpride. CONCLUSIONS: Amisulpride's more pronounced endocrine effects may be a reflection of its distinguished pharmacology and pharmacokinetics.

Adult↗

PubMed1999

Furosemide action on cerebellar GABA(A) receptors in alcohol-sensitive ANT rats.

Furosemide increases the basal tert-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding and reverses the inhibition of the binding by gamma-aminobutyric acid (GABA) in the cerebellar GABA(A) receptors containing the alpha6 and beta2/beta3 subunits. These effects are less pronounced in the alcohol-sensitive (ANT) than in the alcohol-insensitive (AT) rat line. The difference between the rat lines in the increase of basal [35S]TBPS binding was removed after a longer preincubation with ethylendiaminetetraacetic acid (EDTA) containing buffer, but long preincubation did not reduce the GABA content of the incubation fluid or remove the difference in GABA antagonism by furosemide. The GABA sensitivity of the [35S]TBPS binding did not differ between the rat lines. There was no nucleotide sequence difference in the beta2 or beta3 subunits between the rat lines and similar beta2/3 subunit-dependent agonistic actions by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) in the rat lines were detected. The data suggest that there are still unknown structural alterations in the cerebellar GABA(A) receptors between the AT and ANT rat lines, possibly associated with differential alcohol sensitivity.

Alcoholism↗

PubMed1999

Addition of low-dose fluvoxamine to low-dose clozapine monotherapy in schizophrenia: drug monitoring and tolerability data from a prospective clinical trial.

Combining fluvoxamine and clozapine may be a strategy to improve therapeutic effects on negative symptoms in schizophrenic patients. Fluvoxamine, however, markedly inhibits the metabolism of clozapine, and hazardous side effects may result. This study prospectively investigated the safety and tolerability of an add-on therapy with fluvoxamine to a clozapine monotherapy in schizophrenic patients. Sixteen schizophrenic patients received 50 mg fluvoxamine as a comedication after having reached steady-state conditions under clozapine monotherapy. Patients were monitored for subjective adverse events, laboratory parameters, EEG and ECG recordings, orthostatic hypotension and their psychopathology. Concomitantly, serum concentrations of clozapine and metabolites were measured during monotherapy and after addition of fluvoxamine. In all patients, the serum concentrations of clozapine and metabolites were markedly increased (average: 2-3 fold, up to 5 fold for clozapine) after addition of fluvoxamine. Side effects remained almost unchanged in frequency and severity in spite of the pharmacokinetic interactions. ECG or laboratory parameters and orthostatic tests were similar under monotherapy and comedication. Minimal increases of EEG abnormalities were observed, but they were not associated with clinical impairment. Epileptic activities were always absent. The psychopathology improved which continued after start of the comedication. Though the addition of fluvoxamine to clozapine medication was well tolerated and critical side effects were absent, the combined treatment should be controlled by drug monitoring, as serum concentrations of clozapine increased to unpredictably high levels. Further studies have to find out if the combined treatment could be advantageous to clozapine monotherapy.

Adolescent↗

PubMed1998

Combination treatment with clozapine and paroxetine in schizophrenia: safety and tolerability data from a prospective open clinical trial.

Clozapine is a drug with many side effects, some of them with potentially hazardous outcome (e.g. seizures, agranulocytosis), if not carefully monitored. It has been shown that the metabolism of clozapine may be affected by concomitant treatment with selective serotonin reuptake inhibitors (SSRIs), while there have been reports of improved efficacy on negative symptomatology of clozapine in combination with SSRIs. Therefore, this prospective open clinical trial was performed to investigate the safety and tolerability of the coadministration of clozapine and paroxetine under control of serum concentrations of clozapine and its metabolites and the effect of this combination treatment on psychopathological outcome was evaluated. A total of 14 patients suffering from schizophrenia or schizodepressive disorder with predominant negative symptomatology were included. The duration of the study was at least 6 weeks for each patient. Initial treatment was a monotherapy with clozapine at a daily dose of 2.5 mg/kg weight. After two measurements of serum concentrations of clozapine and metabolites during steady state conditions, an add-on therapy with 20 mg paroxetine was initiated. No concomitant medication was allowed. The main finding of our prospective study was that addition of paroxetine to a monotherapy with clozapine was a well tolerated medication that did not give rise to new clinically relevant side effects. After addition of paroxetine the serum concentrations of clozapine and its major metabolites remained virtually constant. The results of the psychopathological measurements indicated a further clinical improvement, although the small open study could not test for efficacy.

Adult↗

PubMed1998

Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: differential effects of fluvoxamine and paroxetine in a prospective study.

Pharmacokinetic interactions of clozapine and its metabolites N-desmethylclozapine and clozapine N-oxide with the selective serotonin reuptake inhibitors (SSRIs) fluvoxamine and paroxetine were investigated in a prospective study in schizophrenic patients under steady-state conditions. Thirty patients were treated with clozapine at a target dose of 2.5 to 3.0 mg/kg of body weight. After gradual dose escalation, serum concentrations of clozapine and two metabolites were determined twice at 7-day intervals after steady-state conditions had been reached. Then, fluvoxamine (50 mg/day) or paroxetine (20 mg/day) was added in 16 and 14 patients, respectively. Serum concentrations of clozapine and its metabolites were measured after 1, 7, and 14 days of coadministration with the SSRI. Mean trough concentrations of steady-state serum concentrations of clozapine, N-desmethylclozapine, and clozapine N-oxide were markedly elevated under fluvoxamine by about threefold of baseline concentrations whereas paroxetine induced only minor, nonsignificant changes. Estimation of the mean elimination half-life of clozapine 2 weeks after start of fluvoxamine comedication revealed an increase from 17 hours to about 50 hours whereas there was no change under paroxetine coadministration. The N-desmethylclozapine/clozapine ratio did not change significantly with either SSRI. Under monotherapy, clozapine mean serum concentrations in smokers were significantly lower by 32% compared with nonsmokers. Similarly, N-demethylation ratios were about 20 to 50% higher in smokers. Thus, in all patients, fluvoxamine induced relevant increases in serum concentrations of clozapine and its metabolites, probably by the inhibition of enzymes catalyzing the degradation of clozapine and N-desmethylclozapine, whereas paroxetine, at a usual clinically effective dosage of 20 mg/day, did not cause significant pharmacokinetic interactions.

Adolescent↗

PubMed1998

Activity of the adenylyl cyclase in lymphocytes of male alcoholic patients is state dependent.

A decreased basal and/or stimulated activity of the G-protein/adenylyl cyclase (AC) system in peripheral blood cells has been proposed to represent a trait marker for alcoholism. However, AC activity may underlie state-dependent changes, which may impair a proper interpretation of AC activity measurements. Our study examined systematically the AC activity in peripheral lymphocytes of 73 male alcohol-dependent patients (according to DSM-IV criteria) at three different time points of measurement during the clinical course of detoxification (day 0 = at admission, while still ethanol-affected; day 2 = at the presumed peak of withdrawal symptoms; day E = after detoxification). Basal and stimulated (with GTPgammaS and forskolin) AC activities were measured. AC activities were compared to those of a control group of 44 healthy male age-matched volunteers. As our main finding, we detected a significant decrease in AC activity from day 0 to day 2 (during withdrawal), with lowered AC activities in a vast majority of patients. This effect resolved after detoxification, as AC activities showed a significant increase from day 2 to E. No significant difference was detected between day 0 and E in AC activities of the patients. Compared with controls, AC activities in patients were significantly lower at day 2, but not at day 0 and E. Taken together, our results indicate rapid and marked state-dependent changes of AC activities in alcohol-dependent patients during the course of detoxification. For an adequate interpretation of AC activities in alcoholic patients, their clinical status must be taken into consideration.

Adenylyl Cyclases↗

PubMed1993

Intracellular ADP activates ATP-sensitive K+ channels in vascular smooth muscle cells of the guinea pig portal vein.

Vasodilatation following tissue ischemia is assumed to partially result from activation of ATP-dependent K+ channels (KATP). To assess the effect of cytosolic adenosine nucleotides, the balance of which depends on tissue pO2, on KATP, we have measured steady state outward currents (SSC) by the whole-cell clamp technique in smooth muscle cells of the guinea pig portal vein at different concentrations of ATP and ADP in the pipette solution. Glibenclamide, a selective inhibitor of KATP, was used as a pharmacological tool. With no nucleotides in the pipette solution (Ca(2+)-free), the SSC determined at +20 mV was unaffected by glibenclamide, while with 0.1 mM ATP or with 0.1 mM ADP, the SSC exhibited a glibenclamide-sensitive component indicating activation of KATP. At 5 mM ATP and no ADP, hardly any effect of glibenclamide on the SSC was detected, suggesting inhibition of KATP by this high concentration of ATP. With 0.1 mM ADP at 5 mM ATP however, activation of KATP was achieved. At 10(-7) M Ca2+ in the pipette solution, an increased SSC was measured, but the responses to the nucleotides and/or glibenclamide were not modified. These findings suggest that in vivo, ADP may be involved in the regulation of vascular KATP, linking tissue pO2 with vascular tone and tissue perfusion.

Adenosine Diphosphate↗

PubMedDate not supplied

Adenylyl cyclase activity is increased in younger, but decreased in older, alcoholic patients after detoxification.

Acute and chronic administration of ethanol leads to alterations of the adenylyl cyclase (AC) signal transduction pathway. This study examined whether the formation of cAMP by AC in lymphocytes correlates with age in alcoholic patients and in healthy controls. Blood was drawn for preparation of lymphocyte membranes and for determination of basal, GTPgammaS-stimulated, and forskolin-stimulated AC activity from 68 actively drinking alcoholic patients (age, mean +/- SD: 45 +/- 10; range: 26-69 years) after ethanol detoxification. The patients' AC activity correlated negatively with age. In contrast, no effect of age was observed in the healthy controls (age, mean +/- SD: 42 +/- 11; range: 24-65 years). The age-related decrease in AC activity of alcoholic patients could not be attributed to the duration of regular alcohol intake. It was partly due to the large variance of AC activity in younger and middle-aged alcoholics.

Adenylyl Cyclases↗

PubMedDate not supplied

Vitamin B12 and hepatic enzyme serum levels correlate in male alcohol-dependent patients.

- Vitamin B12 serum levels and markers for alcohol consumption were determined in 80 male alcohol-dependent patients. Spearman correlation coefficients (r(S)) were calculated. Significant positive correlations between vitamin B12 and hepatic enzyme values were found (gamma-glutamyltransferase: r(S) = 0.58; alanine aminotransferase: r(S) = 0.43; aspartate aminotransferase: r(S) = 0.47; glutamate dehydrogenase: r(S) = 0.43; all P: < 0.001). Therefore, for a proper interpretation of vitamin B12 levels, it may be clinically relevant to take markers of hepatocellular damage into account.

Adult↗

PubMedDate not supplied

Neuropsychological status of alcohol-dependent patients: increased performance through goal-setting instructions.

AIMS: The effects of goal-setting instructions on neuropsychological performance of alcohol-dependent patients and control subjects were assessed. METHODS: 57 alcohol-dependent patients and 59 carefully age- and education-matched healthy control subjects underwent standard neuropsychological investigation. In addition, the goal-setting paradigm was used to systematically manipulate motivation. Participants were requested to calculate simple mathematical problems repeatedly within phases of a 2-min duration receiving normal or goal setting-instructions (to increase performance in the next phase by 20%). RESULTS: The patients demonstrated deficits in standard neuropsychological tests. Patients under goal-setting instructions demonstrated significantly higher improvement (correct responses: P = 0.016) relative to patients with standard instructions. Control subjects with goal-setting instructions demonstrated tendencies for higher improvement relative to control subjects with normal instructions. However, the differences were not significant. Interaction of group (patients vs. control subjects) and instructions (goal setting vs. normal) remained insignificant (P = 0.489) indicating that the increase through goal setting for the patients was not significantly higher than that for the control subjects. CONCLUSIONS: Despite of neuropsychological deficits in reasoning and psychomotor functioning, alcohol-dependent patients early in recovery are responsive to goal setting and able to increase neuropsychological performance. Therefore, goal-setting strategies might possibly be used in cognitive rehabilitation and therapy of alcohol-dependent patients. As there was no significant interaction in increase between patients and control subjects, our results do not support the hypothesis that the neuropsychological deficits are affected by or even caused by motivational limitations of the alcohol-dependent patients.

Adult↗